Role of human papillomavirus genotype in prognosis of early-stage cervical cancer undergoing primary surgery
Role of human papillomavirus genotype in prognosis of early-stage cervical cancer undergoing primary surgery
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DOI：
10.1200/jco.2007.11.2995
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发表时间：
2007-08-20
影响因子：
45.3
通讯作者：
Chang, Ting-Chieh
中科院分区：
文献类型：
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作者：
Lai, Chyong-Huey;Chang, Chee-Jen;Chang, Ting-Chieh
目的探讨人乳头状瘤病毒(HPV)基因分型在大型三级转诊医学中心早期宫颈癌手术治疗中的预后意义。采用聚合酶链式反应(PCR)对38种HPVDNA进行一次聚合酶链式反应(PCR)和反向印迹检测。采用E6型特异性聚合酶链式反应对多个基因分型进行验证。95.1%的标本检测到HPVDNA序列，其中9.6%的标本含有多种类型。HPV16型占63.8%，HPV18型占16.5%。存活患者的中位随访期为77个月。多因素分析显示，FIGO分期、淋巴结转移、宫颈间质侵犯深度、分化程度和HPV18阳性与肿瘤复发显著相关。FIGO II期、深层间质侵犯、宫旁侵犯、HPV18阳性和年龄大于45岁是死亡的重要预测因素。利用从无复发或总体生存分析中选取的7个变量，建立死亡预测模型(P<；.0001)和复发预测模型(P<；.0001)，将其分为低、中、高三个风险组，并进行内部验证。预测模型可用于在未来的临床试验中对患者进行咨询和分层。
PurposeOur aim was to evaluate the prognostic significance of human papillomavirus ( HPV) genotype in early-stage cervical carcinoma primarily treated with surgery in a large tertiary referral medical center.Patients and MethodsConsecutive patients who underwent primary surgery for invasive cervical carcinoma of International Federation of Gynecology and Obstetrics ( FIGO) stage I to IIA between 1993 and 2000 were retrospectively reviewed. Polymerase chain reaction ( PCR) using a general primer set followed by reverse-blot detection of 38 types of HPV DNA in a single reaction was performed for genotyping. E6 type-specific PCR was performed to validate multiple types.ResultsA total of 1,067 eligible patients were analyzed. HPV DNA sequences were detected in 95.1% of the specimens, among which 9.6% contained multiple types. HPV 16 was detected in 63.8% of the samples, and HPV 18 was detected in 16.5% of the samples. The median follow-up time of surviving patients was 77 months. By multivariate analysis, FIGO stage, lymph node metastasis, depth of cervical stromal invasion, grade of differentiation, and HPV 18 positivity were significantly related to cancer relapse. FIGO stage II, deep stromal invasion, parametrial extension, HPV 18 positivity, and age older than 45 years were significant predictors for death. Using the seven selected variables from either recurrence-free or overall survival analysis, death-predicting ( P < .0001) and relapse-predicting ( P < .0001) models classifying three risk groups ( low, intermediate, and high risk) were constructed and endorsed by internal validation.ConclusionThe independent prognostic value of HPV genotype is confirmed in this study. The prognostic models could be useful in counseling patients and stratifying patients in future clinical trials.